Genetic Variant LACTB:p.Ser77Pro (chr15-63122100-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032857.5(LACTB):c.229T>C(p.Ser77Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S77T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LACTB
NM_032857.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.04

Publications

0 publications found

Variant links:

Genes affected

LACTB (HGNC:16468): (lactamase beta) This gene encodes a mitochondrially-localized protein that has sequence similarity to prokaryotic beta-lactamases. Many of the residues responsible for beta-lactamase activity are not conserved in this protein, suggesting it may have a different enzymatic function. Increased expression of the related mouse gene was found to be associated with obesity. Alternative splicing results in multiple transcript variants encoding different protein isoforms. [provided by RefSeq, Dec 2013]

LACTB links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.084368765).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032857.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LACTB	NM_032857.5	MANE Select	c.229T>C	p.Ser77Pro	missense	Exon 1 of 6	NP_116246.2
LACTB	NM_171846.4		c.229T>C	p.Ser77Pro	missense	Exon 1 of 5	NP_741982.1	P83111-2
LACTB	NM_001288585.2		c.229T>C	p.Ser77Pro	missense	Exon 1 of 5	NP_001275514.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LACTB	ENST00000261893.9	TSL:1 MANE Select	c.229T>C	p.Ser77Pro	missense	Exon 1 of 6	ENSP00000261893.4	P83111-1
	LACTB	ENST00000413507.3	TSL:1	c.229T>C	p.Ser77Pro	missense	Exon 1 of 5	ENSP00000392956.2	P83111-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1319108

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

649288

African (AFR)

AF:

0.00

AC:

AN:

26444

American (AMR)

AF:

0.00

AC:

AN:

26636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22298

East Asian (EAS)

AF:

0.00

AC:

AN:

29244

South Asian (SAS)

AF:

0.00

AC:

AN:

72154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32266

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3896

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1051454

Other (OTH)

AF:

0.00

AC:

AN:

54716

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0088

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.32

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.084

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

-1.0

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.59

REVEL

Benign

0.032

Sift

Benign

0.11

Sift4G

Uncertain

0.035

Polyphen

0.0

Vest4

0.13

MutPred

0.23

Gain of catalytic residue at S77 (P = 0.0012)

MVP

0.24

MPC

0.42

ClinPred

0.044

GERP RS

0.078

PromoterAI

0.029

Neutral

(source)

Varity_R

0.16

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over